Pathogenesis and Prognosis of Skin Diseases Caused by Host Immune Responses against EB virus Latent Infections

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1) The spectrum of EB virus (EBV)-associated NK/T-cell. lymphoproliferative disorders (LPD): We have registered cases with EBV-asscciated LPD as a reviewing center, and clarified the disease spectrum and the prognoses (Arch Dermatol 2006, Eur J Dermatol 2006). We have established a website registration system for cutaneous lymphomas, and began to collect the epidemiological data.2) Gene expression analysis using a noninvasive diagnostic method: We have established a noninvasive method using crusts for detection of latently infected EBV and cellular gene products (PATENT PCT/JP2006/317851). This method is available for analysis of other herpesvirus infections and cellular gene expression.3) Evidence for EBV reactivation in the skin legions, and alteration of latency patterns: Patients with severe diseases expressed a reactivation signal (BZLF-1 mRNA) in the skin lesions, while patients with mild diseases did not. In the mild disgase, however, LMP-1 expression levels were increased as compared with those in peripheral blood. 4) Analysis of EBV-infected cell line cells: We performed cytological analysis on the established cell lines. PMA and certain cytokines successfully induced reactivation in EBV-infected.NK/T-cell clones with a latent-infection cycle.5) Host immune responses: We found that pathogenic significance of host ea, responses against various EBV gene products was essential in the development of the skin lesions.6) Therapeutic approach: Host immune responses evoked to C/T antigens were analysed (Int J Cancer 2007). Immune ivasion mechanisms were studied in the same model (Cancer Immunol Immunother 2006). We found that some EBV-infected cells were sensitive to HDAC inhibitors. These observations may provide valuable data for immunopharmacological treatments for EBV-related LPD.7) We have drown out the version of guideline for cutaneous lymphomas including EBV-associaiated LPD.